Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
M Sato, W Grasser

Abstract

The bisphosphonates 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), 3-amino-1,1-hydroxypropane-1,1-diphosphonic acid (APD), and 1-hydroxyethane-1,1-diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. Based on area analysis, the bisphosphonates were effective for the range 10(-7)-10(-8) M, with ABP about two to five times more effective than EHDP or APD. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10(-9) M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 10(2) times higher than the resorption EC50. These data plus immunofluorescence, SEM, a...Continue Reading

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Citations

Jan 1, 1990·Cell Motility and the Cytoskeleton·M Sato, W Grasser
Jan 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S J HunterC V Gay
Jan 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R S EvelyT J Martin
Apr 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J G SeedorD D Thompson
Sep 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·R C MühlbauerH Fleisch
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Jul 1, 1994·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M J RogersF H Ebetino
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